Dataset Information

Altered expression of miRNA-21 and its targets in the hippocampus after traumatic brain injury.

ABSTRACT: Traumatic brain injury (TBI) initiates many different signaling cascades throughout the brain that impact both pathophysiological and neuroprotective processes. Cellular mechanisms that can modulate these processes may play an important role in determining the nature and extent of the damage suffered after TBI and therefore influence overall outcome after injury. MicroRNAs (miRNAs) are an important class of noncoding regulatory RNAs providing an epigenetic mechanism for the regulation of protein expression levels of target genes. We report that miR-21 expression is significantly up-regulated in the hippocampus after rodent TBI, with expression levels peaking by 3 days postinjury and returning to near sham levels by 15 days postinjury. In situ localization of miR-21 transcripts indicates widespread expression in normal brain, with a pronounced increase in expression after TBI evident throughout the cortex and hippocampus, including the dentate gyrus and CA3 cell layer. We used a combination of the miRanda, TargetScan, and PicTar prediction algorithms to identify 99 potential target genes that possess miR-21 binding sites within their 3' untranslated regions. Analysis of these genes' annotated Gene Ontology molecular function and biological process terms revealed an overrepresentation of genes involved in enzyme-linked receptor signaling, transcriptional regulation, and developmental processes. These results suggest that increased miR-21 expression in the hippocampus may influence multiple components of TBI pathophysiology.

SUBMITTER: Redell JB

PROVIDER: S-EPMC7958494 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Altered expression of miRNA-21 and its targets in the hippocampus after traumatic brain injury.

Redell John B JB Zhao Jing J Dash Pramod K PK

Journal of neuroscience research 20101208 2

Traumatic brain injury (TBI) initiates many different signaling cascades throughout the brain that impact both pathophysiological and neuroprotective processes. Cellular mechanisms that can modulate these processes may play an important role in determining the nature and extent of the damage suffered after TBI and therefore influence overall outcome after injury. MicroRNAs (miRNAs) are an important class of noncoding regulatory RNAs providing an epigenetic mechanism for the regulation of protein ...[more]

PMID: 21162128

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Project description:Concussive injury (or mild traumatic brain injury; mTBI) can exhibit features of focal or diffuse injury patterns. We compared and contrasted the cellular and molecular responses after mild controlled cortical impact (mCCI; a focal injury) or fluid percussion injury (FPI; a diffuse injury) in rats. The rationale for this comparative analysis was to investigate the brain's response to mild diffuse versus mild focal injury to identify common molecular changes triggered by these injury modalities and to determine the functional pathways altered after injury that may provide novel targets for therapeutic intervention. Microarrays containing probes against 21,792 unique messenger RNAs (mRNAs) were used to investigate the changes in cortical mRNA expression levels at 3 and 24 h postinjury. Of the 354 mRNAs with significantly altered expression levels after mCCI, over 89% (316 mRNAs) were also contained within the mild FPI (mFPI) data set. However, mFPI initiated a more widespread molecular response, with over 2300 mRNAs differentially expressed. Bioinformatic analysis of annotated gene ontology molecular function and biological pathway terms showed a significant overrepresentation of genes belonging to inflammation, stress, and signaling categories in both data sets. We therefore examined changes in the protein levels of a panel of 23 cytokines and chemokines in cortical extracts using a Luminex-based bead immunoassay and detected significant increases in macrophage inflammatory protein (MIP)-1α (CCL3), GRO-KC (CXCL1), interleukin (IL)-1α, IL-1β, and IL-6. Immunohistochemical localization of MIP-1α and IL-1β showed marked increases at 3 h postinjury in the cortical vasculature and microglia, respectively, that were largely resolved by 24 h postinjury. Our findings demonstrate that both focal and diffuse mTBI trigger many shared pathobiological processes (e.g., inflammatory responses) that could be targeted for mechanism-based therapeutic interventions.

Dataset Information

Altered expression of miRNA-21 and its targets in the hippocampus after traumatic brain injury.

Publications

Altered expression of miRNA-21 and its targets in the hippocampus after traumatic brain injury.

Similar Datasets

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